5,164 research outputs found
Host factors do not influence the colonization or infection by fluconazole resistant Candida species in hospitalized patients
Nosocomial yeast infections have significantly increased during the past two decades in industrialized countries, including Taiwan. This has been associated with the emergence of resistance to fluconazole and other antifungal drugs. The medical records of 88 patients, colonized or infected with Candida species, from nine of the 22 hospitals that provided clinical isolates to the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program in 1999 were reviewed. A total of 35 patients contributed fluconazole resistant strains [minimum inhibitory concentrations (MICs) ≧ 64 mg/l], while the remaining 53 patients contributed susceptible ones (MICs ≦ 8 mg/l). Fluconazole resistance was more frequent among isolates of Candida tropicalis (46.5%) than either C. albicans (36.8%) or C. glabrata (30.8%). There was no significant difference in demographic characteristics or underlying diseases among patients contributing strains different in drug susceptibility
Autosomal Dominant Gain-of-function STAT1 Mutation is a Novel Genetic Etiology of Penicillium Marneffei Infection
Symposium / Free Paper 4: ImmunologyConference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesBackground: Penicillium marneffei infection is indigenous to Southeast Asia.
Majority of cases occur in patients with AIDS and secondary immunodeficiencies.
We previously reported 4 HIV-negative children with chronic mucocutaneous
candidiasis (CMC) and severe penicilliosis. Hyper-IgE syndrome was diagnosed
in one of them, but extensive genetic studies on IL12-IFNγ axis, CARD9 and AIRE
were unrevealing for the rest. Recently, STAT1 hyperphosphorylation causing
defective Th1 and Th17 immunity is recognized as a cause of CMC.
Objective: To investigate the genetic and functional defects of STAT1 signaling in
children affected by penicilliosis.
Methods: Targeted sequencing of STAT1 gene or total exome sequencing was
performed in 3 patients with CMC and penicilliosis. PBMCs were isolated from
patients and normal controls. Intracellular STAT1 phosphorylation (pSTAT1)
towards interferon-α and interferon-γ stimulation was evaluated by flow
cytometry. Cytokine production in PBMCs towards PMA and ionomycin stimulation
was assessed. PBMCs were co-cultured with live Candida albicans and
P. marneffei to evaluate interferon-γ response.
Results: Heterozygous STAT1 missense mutations were identified in all 3 patients.
Two mutations were located in the coiled-coil domain (P1 and P2) and one in
the DNA-binding domain (P3). All 3 patients recovered from penicilliosis, but P1
eventually died of fulminant aspergillosis. The percentage of pSTAT1-positive
PBMCs induced by interferon-α and interferon-γ was significantly higher in all
3 patients than normal controls, indicating that they had gain-of-function mutations. PBMCs from all patients displayed defective interferon-γ and
interleukin-17 production towards PMA and PMA plus ionomycin, respectively.
Interferon-γ production induced by C. albicans and P. marneffei in P2 was
significantly lower than normal controls.
Conclusions: For the first time, we demonstrated STAT1 gain-of-function
mutation as an important and novel genetic etiology of invasive mycosis including
penicilliosis and aspergillosis. Penicilliosis should be regarded as an indicator
disease for primary immunodeficiencies in children without HIV infection unless
proven otherwise.published_or_final_versio
Plexin-B1 and semaphorin 4D cooperate to promote perineural invasion in a RhoA/ROK-dependent manner
Perineural invasion (PNI) is a tropism of tumor cells for nerve bundles located in the surrounding stroma. It is a pathological feature observed in certain tumors, referred to as neurotropic malignancies, that severely limits the ability to establish local control of disease and results in pain, recurrent growth, and distant metastases. Despite the importance of PNI as a prognostic indicator, its biological mechanisms are poorly understood. The semaphorins and their receptors, the plexins, compose a family of proteins originally shown to be important in nerve cell adhesion, axon migration, and proper central nervous system development. Emerging evidence has demonstrated that these factors are expressed in tissues outside of the nervous system and represent a widespread signal transduction system that is involved in the regulation of motility and adhesion in different cell types. We believe that the plexins and semaphorins, which are strongly expressed in both axons and many carcinomas, play a role in PNI. In this study, we show that plexin-B1 is overexpressed in tissues and cell lines from neurotropic malignancies and is attracted to nerves that express its ligand, semaphorin 4D, in a Rho/Rho kinase-dependent manner. We also demonstrate that nerves are attracted to tumors through this same system of proteins, suggesting that both plexin-B1 and semaphorin 4D are important in the promotion of PN
Dynamic tracking model for the reservoir water flooding of a separated layer water injection based on a well temperature log
p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.
Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21.published_or_final_versio
Novel OCRL mutations in children with Lowe Syndrome
Background: Lowe syndrome is a rare X-linked recessive hereditary disease caused by mutations of the OCRL gene, which encodes an inositol polyphosphate-5-phosphatase. The disease is clinically characterized by congenital cataracts, psychomotor retardation, and proximal tubulopathy. Methods: We retrospectively reviewed three unrelated Chinese patients with Lowe syndrome, clinically diagnosed by the abnormalities of eyes, nervous system, and kidneys. Genetic analysis of the OCRL gene was done for the three patients as well as their family members. Results: Three OCRL gene mutations were detected in our study. Two of the mutations, g.1897delT in exon 18 (patient 1) and g.1470delG in exon 15 (patient 2), were novel. A missense mutation (p.Y513C) in exon 15, which had been reported previously, was found in patient 3. The mothers of all patients were heterozygous carriers of the respective mutations. Conclusion
Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species
BACKGROUND: Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. METHODS: A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. RESULTS: There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. CONCLUSION: Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC
Two-dimensional universal conductance fluctuations and the electron-phonon interaction of topological surface states in Bi2Te2Se nanoribbons
The universal conductance fluctuations (UCFs), one of the most important
manifestations of mesoscopic electronic interference, have not yet been
demonstrated for the two-dimensional surface state of topological insulators
(TIs). Even if one delicately suppresses the bulk conductance by improving the
quality of TI crystals, the fluctuation of the bulk conductance still keeps
competitive and difficult to be separated from the desired UCFs of surface
carriers. Here we report on the experimental evidence of the UCFs of the
two-dimensional surface state in the bulk insulating Bi2Te2Se nanoribbons. The
solely-B\perp-dependent UCF is achieved and its temperature dependence is
investigated. The surface transport is further revealed by weak
antilocalizations. Such survived UCFs of the topological surface states result
from the limited dephasing length of the bulk carriers in ternary crystals. The
electron-phonon interaction is addressed as a secondary source of the surface
state dephasing based on the temperature-dependent scaling behavior
Activation of NAG-1 via JNK signaling revealed an isochaihulactone-triggered cell death in human LNCaP prostate cancer cells
One-dimensional Topological Edge States of Bismuth Bilayers
The hallmark of a time-reversal symmetry protected topologically insulating
state of matter in two-dimensions (2D) is the existence of chiral edge modes
propagating along the perimeter of the system. To date, evidence for such
electronic modes has come from experiments on semiconducting heterostructures
in the topological phase which showed approximately quantized values of the
overall conductance as well as edge-dominated current flow. However, there have
not been any spectroscopic measurements to demonstrate the one-dimensional (1D)
nature of the edge modes. Among the first systems predicted to be a 2D
topological insulator are bilayers of bismuth (Bi) and there have been recent
experimental indications of possible topological boundary states at their
edges. However, the experiments on such bilayers suffered from irregular
structure of their edges or the coupling of the edge states to substrate's bulk
states. Here we report scanning tunneling microscopy (STM) experiments which
show that a subset of the predicted Bi-bilayers' edge states are decoupled from
states of Bi substrate and provide direct spectroscopic evidence of their 1D
nature. Moreover, by visualizing the quantum interference of edge mode
quasi-particles in confined geometries, we demonstrate their remarkable
coherent propagation along the edge with scattering properties that are
consistent with strong suppression of backscattering as predicted for the
propagating topological edge states.Comment: 15 pages, 5 figures, and supplementary materia
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